Rationale: In an earlier study, clinically unrecognized immunodysregulation and protein-losing enteropathy were identified in nursing home residents treated with antibiotics. Those antibiotic recipients who were also treated with bismuth subsalicylate had a statistically significant decreased death rate as compared to antibiotic recipients who were not concurrently treated with bismuth subsalicylate. In addition, there was a nonsignificant tendency for the group treated with bismuth subsalicylate to have a lower incidence of stool protein loss. The potential mechanisms by which bismuth subsalicylate might affect mortality and/or loss of protein across the gastrointestinal mucosa would involve: 1) the systemic anti-inflammatory effects of the salicylate moiety; and/or 2) the local protective and/or antibiotic effects of the unabsorbed bismuth moiety. The proposed project was undertaken to provide corroboration of the results of the original study, which was halted when the increased death rate was identified in the control group, and to determine whether the systemic anti-inflammatory effects of the salicylate moiety and/or the protective/antibacterial effects of the bismuth moiety underlie a decreased death rate among antibiotic recipients treated with bismuth subsalicylate and/or aspirin as compared to placebo. Specific Aims: The specific aims of this projects were to determine whether concurrent treatment of antibiotic recipients with bismuth subsalicylate or aspirin decreases the following outcomes: 1) death rates within 7, 14, and 30 days following antibiotic prescription; 2) prevalence of protein-losing enteropathy within 7, 14, and 30 days following antibiotic prescription; 3) levels of plasma cytokines, e.g., tumor necrosis factor (TNF), interleukin-2 receptor (IL-2R), etc. within 7, 14, and 30 days following antibiotic prescription. Study design: Partially blinded, randomized, prospective comparison trial. Randomization was done by unblocked allocation using a table of random numbers. Intervention: Bismuth subsalicylate 30 ml, four times per day for 21 days (1040mg salicylate total daily dose) versus aspirin, 325 mg three times per day for 21 days (975mg salicylate total daily dose) versus placebo three times per day for 21 days for antibiotic recipients enrolled within 72 hours of initiating antimicrobial therapy. Enrollees were monitored for 30 days following the initial prescription of antibiotics. Results: A total of 111 subjects were enrolled (36 in the bismuth subsalicylate group, 38 in the aspirin group, and 37 in the placebo group). Eighty-four subjects completed the study (27 in the bismuth subsalicylate group, 30 in the aspirin group, and 27 in the palcebo). Two subjects died (one placebo and one aspirin group). Preliminary data analyses revealed 11 subjects with positive C.difficile cultures (4 in the bismuth subsalicylate group, 2 in the aspirin group and 5 in the placebo group). Stool specimens are currently being analyzed for alpha-1 antitrysin and lactoferrin.